The objective of this proposal is to determine the cellular basis for changes in pituitary gonadotrope responsiveness to gonadotropin releasing hormone (GnRH) in the normal aging rat. The gonadortrope produces luteinizing hormone and follicle stimulating hormone which, in turn, regulate reproductive function and steroidogenesis. A large body of information suggests that changes in reproductive function in senescence is correlated with specific changes in pituitary respnsiveness to GnRH and the chemical nature of the gonadotropin released. The present study is designed to measure the contribution of specific cellular changes that appear to be the basis of the altered gonadotrope responsiveness. It is probable that changes in GnRH receptor level, coupling of the receptor to the response mechanism, or the response mechanism itself is altered during the normal aging process. Accordingly, we propose to analyze individual steps in the mechanism of gonadotropin production and release during aging in order to develop a model which explains the altered cellular responsiveness which is observed during aging.